Monkeypox: Diagnosis and Treatment

The monkeypox outbreak in the U.S and Europe continues to grow. Below is a summary of the current state of the outbreak in the United States, and the most recent CDC guidelines for diagnosis and treatment. (Please see EMplify podcast on monkeypox, May 23,2022 for background information)

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The CDC reports that U.S. has reached 790 confirmed cases. This places the US fourth in the world for the most cases in a non-endemic country.

Country	Confirmed Cases
United Kingdom	1552
Germany	1490
Spain	1256
United States	790
France	721
Portugal	415
Canada	376

The CDC continues to see the majority of cases in men who have sex with men, but not exclusively. They note that “…anyone who has been in close contact with someone who has monkeypox is at risk.“

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Diagnosis

Diagnosis is based on characteristic symptoms that progress through the following stages:

Incubation: 1-2 weeks, no symptoms

Prodrome

• Fever
• Malaise
• Headache
• Sore throat
• Cough
• Lymphadenopathy.

Rash

Rash	Duration in Days	Appearance
Mucus Membranes	–	Lesions on the tongue and inside the mouth
Macules	1-2	Starting on face and spreading to: -Arms and legs, then -Hands and feet (including palms and soles) Whole body involvement typical by 24 hours, but remains most concentrated on face, arms, and legs.
Papules	1-2	Raised lesions can be felt. Typically by day 3.
Vesicles	1-2	Vesicles containing clear liquid form. Typically by days 4-5.
Pustules	5-7	Vesicles filled with yellow fluid. Round, firm pustules. Typically days 6-7.
Scabs	7-14	Pustules crust and scab over. Typically at end of week two. Scabs remain an additional week. Patient remains contagious until all scabs fall off.

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Treatment

There are 4 possible anti-viral therapies for patients who meet high risk criteria, after consultation with the CDC:

• Severe disease- sepsis, encephalitis, hemorrhagic disease, illness requiring hospitalization.
• Immunocompromised patients – HIV, leukemia, lymphoma, active treatment for cancer, organ transplant, stem cell transplant <24 months > 24 months with graft vs host disease.
• Pediatric patients younger than 8.
• Patients with atopic dermatitis or other skin conditions – eczema, burns, impetigo, varicella zoster, HSV, extensive areas of denuded skin.
• Pregnant or breastfeeding women.
• Patients with complications – secondary bacterial infection, enteritis with severe vomiting or diarrhea, pneumonia.
• Patients with disease in “aberrant” areas – eyes, mouth, genitals, anus.

There is no medication approved specifically for treatment of monkeypox. Current antiviral therapies available from the CDC include:

• Tecovirimat (TPOXX, ST-246) – Antiviral FDA approved for treatment of smallpox in adults and children. Studies in animals show efficacy against other orthopoxviruses.
• Vaccinia Immune Globulin Intravenous (VIGIV)- Approved for treatment of complications from vaccinia vaccine. No evidence for use in monkeypox or other orthopoxviruses. CDC suggests “VIG can be considered for prophylactic use in an exposed person with severe immunodeficiency in T-cell function for which smallpox vaccination following exposure to monkeypox virus is contraindicated.”
• Cidofovir (Vistide) – Antiviral FDA approved for treatment of cytomegalovirus (CMV). No data exists for its use in monkeypox cases. Has show efficacy against other orthopoxviruses in vitro and in animal studies.
• Brincidofovir (CMX001, Tembexa) – Antiviral approved by the FDA for treatment of smallpox in adults and children in 2021. No data exists for its use in monkeypox cases. Has show efficacy against other orthopoxviruses in vitro and in animal studies.

All treatment is guided by the CDC and facilitated through local departments of health. Notify your local department of health for any possible or confirmed case.

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Vaccination

Vaccination recommendations change regularly. Please see the CDC page for up to date guidelines as they change frequently.

Pre-exposure

Currently, there is no recommendation for widespread vaccination of healthcare workers. The CDC does recommend vaccination for workers in clinical and research labs who may come in contact with specimens (specifically for monkeypox testing) and public health response teams who may come in contact with infected patients. Two vaccines are currently in use: ACAM2000 and JYNNEOS.

• ACAM2000 is a live vaccinia virus vaccine given as a single dose. Patients are considered “vaccinated” after 28. Lesions caused by this vaccine contain live virus and can transmit disease.
• JYNNEOS is a live virus, non-replicating, vaccine given as 2 doses 4 weeks apart. Patients are considered “vaccinated” 2 weeks after the second dose.

Post-exposure prophylaxis

• Currently, the CDC recommends post-exposure prophylaxis within 4 days if possible. However, it is offered up to 14 days after exposure to asymptomatic patients.
• Exposed patients who have not received a smallpox vaccine within 3 years are recommended for monkeypox vaccination.

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Exposure

Post-exposure prophylaxis is guided by the degree of exposure. The CDC uses the following 3 categories:

Exposure Category	Characteristics	Recommendation
High	Unprotected contact between a person’s skin or mucous membranes and the skin, lesions, or bodily fluids from a patient (e.g., any sexual contact, inadvertent splashes of patient saliva to the eyes or oral cavity of a person, ungloved contact with patient), or contaminated materials (e.g., linens, clothing) -OR- Being inside the patient’s room or within 6 feet of a patient during any procedures that may create aerosols from oral secretions, skin lesions, or resuspension of dried exudates (e.g., shaking of soiled linens), without wearing an N95 or equivalent respirator (or higher) and eye protection -OR- Exposure that, at the discretion of public health authorities, was recategorized to this risk level (i.e., exposure that ordinarily would be considered a lower risk exposure, raised to this risk level because of unique circumstances)	PEP – Recommended
Intermediate	Being within 6 feet for 3 hours or more of an unmasked patient without wearing, at a minimum, a surgical mask -OR- Activities resulting in contact between sleeves and other parts of an individual’s clothing and the patient’s skin lesions or bodily fluids, or their soiled linens or dressings (e.g., turning, bathing, or assisting with transfer) while wearing gloves but not wearing a gown -OR- Exposure that, at the discretion of public health authorities, was recategorized to this risk level because of unique circumstances (e.g., if the potential for an aerosol exposure is uncertain, public health authorities may choose to decrease risk level from high to intermediate)	PEP – Informed clinical decision making recommended on an individual basis to determine whether benefits of PEP outweigh risks
Low	Entered the patient room without wearing eye protection on one or more occasions, regardless of duration of exposure -OR- During all entries in the patient care area or room (except for during any procedures listed above in the high-risk category), wore gown, gloves, eye protection, and at minimum, a surgical mask -OR- Being within 6 feet of an unmasked patient for less than 3 hours without wearing at minimum, a surgical mask -OR- Exposure that, at the discretion of public health authorities, was recategorized to this risk level based on unique circumstances (e.g., uncertainty about whether monkeypox virus was present on a surface and/or whether a person touched that surface)	PEP – None

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Further Reading

• EMplify Monkeypox podcast
• CDC Monkeypox Guide

Last Updated on January 25, 2023